1. Field of the Invention
The present relates to methods of diagnosing laryngeal cancer or diagnosing prognosis in radioresistance of laryngeal cancer.
2. Description of the Related Art
Radiotherapy is the standard treatment for laryngeal cancer which is the most common cancer occurring on a head and a neck. However, a large number of patients with laryngeal cancer still suffer from local recurrences after radiotherapy, due to the survival of a small fraction of radioresistant tumor cells during the course of radiation therapy.
Thus, to improve the efficacy of radiotherapy, studies have done on drugs that inhibit molecular targets contributing to the radioresistance of tumor cells. Accordingly, it is confirmed that several molecular targets modulate tumor survival and microenvironment have been shown to influence the outcome of radiotherapy. However, relevant targets and signaling pathways are clinically still unclear.
Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that transmits oncogenic signals from cytokines and growth-factor receptors to the nucleus.
Overexpression of STAT3 in response to the aberrant activation of upstream receptor signals is frequently observed in a variety of cancers including head and neck cancer.
Persistent STAT3 activation promotes the growth and survival of tumor cells through modulation of cell cycle regulators, e.g., cyclin D1, cyclin D2, and c-Myc, upregulation of anti-apoptotic proteins, e.g., myeloid cell leukemia-1 (Mcl-1), B-cell lymphoma 2-like 1 (Bcl-xl), and survivin, downregulation of the tumor suppressor p53, and induction of angiogenesis by vascular endothelial growth factor (VEGF). That is, these mechanisms eventually contribute to resistance to anti-cancer drugs.
In addition, recent reports indicate that Janus Kinase (JAK)/STAT signaling contributes to tumor resistance by modulating not only cell survival but also the tumor microenvironment, including tumor hypoxia and immunity.
Thus, studies on STAT3 activation are essential subjects for overcoming tumor resistance to chemotherapy and radiotherapy.
ERp57, which is also known as protein disulfide isomerase family A member 3 (PDIA3) or glucose-regulated protein 58 (GRP58), belongs to the family of protein disulfide isomerases, and is known as a multifunctional chaperone that regulates proper folding of glycoproteins. In addition, ERp57 also participates in the assembly of major histocompatibility complex class 1 in the endoplasmic reticulum (ER).
In the related art, a gene encoding ERp57 or calreticulin (CRT)/caltexin (CNX) protein, a transformant prepared by transfecting a cell producing a target protein with an expression vector containing the gene that encodes ERp57 or CRT/CNX protein, and a method for mass-production of the target protein by culturing the transformant with different concentrations of tetracycline have been disclosed (refer to Patent document 1).
However, the roles of ERp57 and the correlation between ERp57 and STAT3 in laryngeal cancer, especially radioresistant laryngeal cancer, have not been reported yet.